The central goal of this project is to determine aspects of the structure of excitable channels by chemical modification. In the coming year we intend to focus on the effects of internal and external pH, crosslinking reagents and several group specific reagents on the asymmetry currents which are thought to reflect the gating of the sodium channel. The asymmetry currents have several phases which might reflect different reaction steps in a sequential or parallel reaction scheme. How the reagents effect these phases should provide clues on the nature of the underlying mechanism. We wish to also study the effects of high viscosity on gating and drug blockade rates. In particular we wish to study these effects on the sodium channel gating and asymmetry currents.